Aromatase Inhibitor for HRT Monotherapy

Many men in their late 30’s and up are starting to discover the benefits of Hormone Replacement Therapy. As Testosterone levels decline, so does sex drive, strength, muscle mass, and energy levels. At the same time, metabolic syndrome can creep up on the aging male. There are a lot of good reasons an older male should consider restoring his hormone levels to an optimal level. Many men shy away from conventional HRT for a few reasons, however. For many, the idea of messy creams, painful injections, and costly out-of-pocket expenses are enough to keep many from seeking treatment. It seems like the scientific community is coming to realize something many bodybuilders have known for years: Medications that lower Estrogen will increase Testosterone, and in some cases, can raise those levels to supraphysiological levels.

The HPTA (Hypothalamic Pituitary Testicular Axis) is tightly regulated in order to maintain a certain homeostasis. As we age, a number of things happen that begin to skew this perfect balance. The Hypothalamus senses the levels of Androgens (in particular Testosterone) and Estrogens in order to determine whether or not to signal the Pituitary gland to send the signal to the Testes to produce Testosterone. Let’s back up for just a minute… Testosterone can be aromatized, or chemically altered, to become Estrogen. The aromatase enzyme converts Testosterone into Estrogen. A certain amount of Estrogen is crucial to health, while an excess of Estrogen can lead to a few undesirable effects, one of which is the reduction of Testosterone. Remember where I said the Hypothalamus measures the amount of Testosterone AND Estrogen in order to determine how much Testosterone to make? Well, Estrogen levels, even at “normal” levels can keep Testosterone levels down. If you are overweight (aromatase enzymes are abundant in fat tissue, another reason to get lean) or aging, those Estrogen levels will creep up and slowly reduce Testosterone below optimal levels.

Many bodybuilders have learned that lowering Estrogen will increase Testosterone, because over-the-counter Aromatase inhibitor products like Formestane, Epistane, and ATD all promised to increase Testosterone and reduce bloat that comes with Estrogen. And it definitely delivered. Many people found taking these hormonal anti-aromatase products did a great job of increasing Testosterone. Many users were disappointed simply because they hoped that increase in Testosterone would result in rapid strength gains, muscle mass accrual and a reduced waistline. While these products will support these goals, they are no replacement for the get ripped quick promises of prohormones like Methyl-1-Test or Superdrol. For the aging male however, this boost of Testosterone, while not of Hulk-like proportions, will restore a deficit in Testosterone and will most likely increase all of the desired effects that one can hope for.

While many of us have known for years that these drugs will provide a more than modest boost in Testosterone, the scientific community took a while to catch up. There have now been numerous studies showing anti-estrogens like Clomiphene and Anti-Aromatase drugs like Exemestane can produce measurable results, and in some cases these drugs can be used alone, as a monotherapy, for Hormone Replacement Therapy. I guess you would technically call it Hormone Optimization Therapy. Instead of replacing Testosterone through injections or creams, or even sublingual pills, we can trick the body into producing more Testosterone naturally.

So what are the downsides? Well for starters, if you have hypogonadism that is a result of testicular insufficiency (i.e. your testicles are not capable of producing testosterone) then this therapy will be of little use. Testosterone replacement would be warranted in that case. The other side effects for those who do benefit from Estrogen reduction are the same kind of issues menopausal women experience due to the ceasing of Estrogen production. While high Estrogen levels can cause unwanted side effects in men, such as increased fat gain and water retention, Estrogen levels that are too low can cause bone loss, joint pain and cholesterol problems (Lowers HDL while increasing LDL). Some anti-aromatases(arimidex, aka anastrozole) will also decrease IGF-1 which will ultimately lead to reduced benefits from that particular hormone, including insulin sensitivity and fat loss.

There are two different options to go with when controlling for Estrogen. I will give you both examples and then mention my preference.

1) Anti-Estrogens

(Clomiphene, Tamoxifen, Raloxifene)

Anti-Estrogens are actually weak estrogenic compounds themselves. The technical name for these drugs is Selective Estrogen Receptor Modulators, or SERMS. These drugs were actually developed to fight breast cancer. By blocking specific receptors in breast tissue, Estrogen cannot influence the growth of tumors, and yet other types of Estrogen receptors in the body are not affected. In men, Clomid (Clomiphene) along with the other drugs, blocks the Estrogen receptor in the Hypothalamus which prevents Estrogen from binding to it, which then fools the body into thinking it needs to ramp up Testosterone. Even though it does a good job of this in the hypothalamus and breast tissue, it is a weak antagonist, meaning it binds to the receptor but does not send as strong of a signal as Estrogen does, therefore it does not act like Estrogen in the body. Essentially this is a weak Estrogen that only acts on certain receptors in the body, which allows Estrogen to still do its thing where it’s needed, for example in bone density.

1) Aromatase Inhibitors

(Exemestane, Anastrozole, Letrozole, Formestane, ATD)

Aromatase inhibitors act more like a bomb than a sniper like the aforementioned anti-estrogens. Instead of selectively binding to receptors, Aromatase inhibitors inactivate the aromatase enzymes. Within the Anti-Aromatase categories you have several variants. Steroidal (irreversible inhibitors) versus Non-Steroidal (reversible inhibitors). Irreversible steroidal inhibitors, such as Exemestane (Aromasin), forms a permanent and deactivating bond with the aromatase enzyme. Non-steroidal inhibitors, such as anastrozole (Arimidex), inhibit the synthesis of estrogen via reversible competition for the aromatase enzyme. This is a lot of technical stuff here and I’m not going to get lost in the discussion of it, but simply put, irreversible inhibitors completely break the enzyme aromatase, whereas reversible AI like Anastrazole just fuck with the enzyme for a while and eventually “let it go” for lack of a better term. In reality, there is no major difference in aromatase control when discussing the benefits of either. But what I do know is that the irreversible AI Exemestane does a better job in two areas.

Benefits of Exemestane:

Little change or positive increase in IGF-1 Levels

Relatively benign effect on lipids (hdl and ldl cholesterol)

Benefits of Letrozole:

Much stronger suppression of Estrogen

Better for Gynecomastia control (breast growth in men)

So for the purpose of damage control, many bodybuilders who use Anabolic substances will take an AI like Letrozole to really crush Estrogen. This stops the process of breast growth and in some cases can actually reduce breast tissue. The downside of this is that it also “drys out” the joints, decreases bone density and screws with Cholesterol levels. So in my opinion, Letrozole and Anastrazole should be used only for a short period of time, or used at low dosages in order to avoid some of the harsher effects. If Gynecomastia is an issue, then look into using Letro in larger doses for a short period of time. OR, as I always recommend, just get the surgery. In the long run, having a plastic surgeon who knows what they’re doing will be a much better investment in cosmetic and physical health than running long periods of AI’s that will wreak havoc on IGF-1, bone density and Cholesterol.

For the purpose of Hormonal Optimization, I recommend Exemestane. It is gentler, will only reduce Estrogen to within healthy range, will keep IGF-1 levels consistent, and will leave lipid levels relatively unscathed.

As for the argument of Anti-Estrogen versus Aromatase Inhibitor, I would seriously suggest sticking with an AI such as Exemestane. You will get the added benefit of reduced water retention which will not be seen with anti-estrogens like tamoxifen, and you will keep your IGF-1 levels in check. If you are a female with breast cancer you most indubitably need to be lowering IGF-1. It will decrease the growth of cancerous cells. But in men trying to maintain their physique and health, using something which leaves IGF-1 levels alone is a much better option.

NOW…

Am I telling you to go out and buy a bunch of Anti-Aromatase and just start pounding it? Absolutely not. This is something you need to speak with your doctor about. It’s absolutely vital to monitor your progress and regularly test your Testosterone levels (both total Test and free Test), your Estrogen levels (remember, we don’t want to crush it, just reduce it), your IGF-1 levels, and finally your Cholesterol levels. Without this regular monitoring you are jeopardizing your health and you could also be compromising your gains!

Ok, so one last thought on this. If you are serious about looking into this, you will need to find a doctor that is open to this kind of treatment. By far, the biggest issue I hear about when it comes to HRT treatment that veers away from the mainstream Testosterone Creams and such, is that most doctors are ignorant of this type of protocol. Many of them will scoff at your suggestion and tell you that AI’s and Anti-Estrogens are only for women who have breast cancer. If you present your doctor with a few studies showing that it has been used effectively to treat hypogonadism and they still don’t budge, then perhaps you need to find a new doctor. Sometimes people think endocrinologists would be the best people to go to, but in a lot of instances, they are very set in their ways. Unless they are fresh out of school, they may be holding on to the old paradigm of Testosterone injections. And in some cases, Testosterone injections will be the best way to go. If you have liver problems or bone density issues, then perhaps Testosterone injections will be optimal, because it will actually increase your Estrogen levels which will help with bone density and maintaining cholesterol. These are issues you need to test for and you need a skilled and licensed medical professional to help guide you through this process.

Comments

I take arimidex as part of my TRT regime. I recently switched over from axiron gel to injectible at 250mg every 5 days (so yeah, a bit more than TRT, almost cycle) and just got labs back with 1400 total T and e2 at 20 or so, which seems to be in range. But I do believe last week or so I used arimidex at a bit too high of a dose and suffered terrible depression for a few days. I’m also not too keen on the reduction in IGF-1. Would Exemestane do a similar job as arimidex when one is on TRT or a low grade cycle? Would it be a better choice because it doesn’t affect IGF1 levels as much? Would be willing to try. Also curious why you didn’t mention toremifne?

Actually, I completely misspoke, and it’s a good thing I don’t confess to be a guru. It appears that AI’s like Anastrozole increase IGF-1 while SERMs like Nolvadex lower it. So any Aromatase inhibitor would be a safe bet insofar as IGF-1 levels are concerned.

You’re right, taking too much of an AI will induce depression, loss of sex drive and increased joint pain and muscle stiffness. We want a normal, slightly lowered estrogen level. Crushing it is just as detrimental in my opinion.

Exemestane is a really good choice for men wanting to control IGF-1 because it does so more gently. It will not eradicate estrogen as greatly as Arimidex or Femara. So the benefit with Exemestane is the decreased likelihood of lowering Estrogen too much.

I didn’t mention Toremifene because I forgot to, honestly. It is a pretty good protective drug for gynecomastia, but in some ways, Clomiphene is still superior with regards to its effect on HPTA, which is the focus of this article.

Thanks for the article. I was wondering if you had a good way to track down some of these doctors who are willing to work with HRT. I live on the east coast and have a doc on the west coast I could use, but would rather not have to fly to see someone. If you know of a list of people I’d really appreciate seeing it.